Inertia, Intensification and Incretins
04 Sep 2023
byJoanne G. Blanco, MD
In the realm of modern medicine, the term "clinical inertia" has gained significant attention for its potential to hinder effective disease management. Within the context of diabetes management, clinical inertia refers to the delay or reluctance in intensifying therapy despite clear indications for doing so, such as not achieving their target HbA1c goal.1 Fortunately, a new era is dawning in diabetes treatment, and incretin therapy with GLP1 receptor agonists (GLP1-RAs) like Dulaglutide is emerging as a pivotal solution for breaking through the constraints of clinical inertia.
Clinical Inertia: Unraveling the hindrance
Clinical inertia or therapeutic inertia is a multifaceted challenge that can be caused by patient-related, physician-related, or healthcare system-related factors (Figure 1). It spans across various medical specialties, but its implications are especially pronounced in the realm of diabetes management. It can occur when healthcare providers fail to adequately adjust treatment plans despite clear indications that current therapies are insufficient in achieving desired clinical outcomes.1,2
Figure 1. Multiple factors that lead to clinical or therapeutic inertia. (Adapted from Okemah et al, 2018)
On the other hand, patients who are reluctant to intensify treatment due to lack of awareness of the progressive nature of the disease or poor glycemic control also contribute a lot to the development of clinical inertia. While patient-related and physician-related causes are common, healthcare system-related factors in countries with limited resource are as challenging. In diabetes care, these often translate to delay in intensification of treatment, thereby allowing the disease to progress unchecked.1 Clinical inertia perpetuates the vicious cycle of escalating complications and reduced quality of life for patients. This phenomenon can lead to suboptimal control of blood glucose levels and subsequent complications.2
Intensification of Diabetes Therapy: Shifting Paradigms
Historically, the initiation of injectable therapy was often delayed until oral medications and lifestyle interventions yielded inadequate results.3 However, recent guidelines and evolving evidence suggest a more proactive approach to therapy intensification. Early initiation of injectable therapy, including GLP1-RAs, has shown promise in achieving and sustaining glycemic control, reducing the risk of complications, and minimizing the impact of clinical inertia.
The recent ADA/EASD Consensus Statement has brought focus to the use of glucose-lowering medications in consideration of clinically important factors, with greater emphasis on weight management as part of the holistic approach to management as well as broader recommendations for cardiorenal protection in people at high risk of cardiorenal disease. The need to reassess and modify treatment regularly (3-6 months) to avoid therapeutic inertia was also emphasized.4
Navigating Patient Hesitancy Towards Injectable Therapy
One of the key challenges in diabetes management is patient hesitancy toward injectable therapies.5 Fear of needles, concerns about the complexity of injections, and apprehensions about the perceived invasiveness of injectable treatments often deter patients from embracing these options. As medical professionals, fostering open and empathetic communication is vital to addressing these concerns and motivating patients to take the necessary steps towards improved glycemic control.5,6
Advantages of GLP1-RAs: Empowering Intensification
Among injectable therapies, GLP1-RAs have emerged as a cornerstone of intensification strategies being alternatives to basal insulin over the past 10 years. These are incretin mimetics that reproduce the effects of endogenous glucagon-like peptide-1 and, as such, stimulate glucose-dependent pancreatic insulin secretion and suppress pancreatic glucagon.7 The recent ADA and EASD consensus guidelines list GLP1-RAs as alternatives to insulin for treatment intensification in patients inadequately controlled with oral antidiabetic drugs.4 GLP-1 RAs also demonstrated significant benefits for both glycemic control and weight management over additional oral antidiabetic drugs (OADs) or insulin, respectively.8 Moreover, unlike traditional insulin therapy, GLP1-RAs offer distinct advantages in terms of convenience, efficacy and cardiovascular and renal benefits.9
The REWIND Trial has provided compelling evidence of the cardiovascular benefits associated with dulaglutide. Notably, this trial demonstrated a significant reduction in 3-point major cardiovascular event (MACE-3), a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, in patients with type 2 diabetes both with or without established CVD.9 These findings underscore the potential for GLP-1 RAs, particularly dulaglutide, to provide multifaceted benefits beyond glycemic control, further motivating early intervention and overcoming clinical inertia.9,10
An additional characteristic of dulaglutide resides in its prolonged half-life of approximately 5 days. This prolonged duration permits a once-weekly administration regimen, a notable advantage when juxtaposed with certain GLP1-RAs necessitating daily dosages.11,12 The less frequent treatment schedule offered by dulaglutide augments patient convenience and compliance, effectively alleviating the daily injection burden.13
Furthermore, within a comparative study gauging the temporal precision, usage accuracy, participant contentment, and preferences concerning pen devices employed for the once-weekly GLP-1 RAs dulaglutide, exenatide, and semaglutide, a substantial majority (75%) of participants evinced a clear inclination towards the dulaglutide device, signifying an overarching preference.13
Empirical evidence underscores the favorable attributes of dulaglutide in relation to other GLP-1 RAs. Notable investigations have demonstrated that dulaglutide garners superior reductions in HbA1c levels when pitted against liraglutide.12 Additionally, it exhibits heightened adherence rates in comparison to both exenatide and liraglutide.13
As a GLP-1 RA, the most common adverse effects are mild and transient gastrointestinal manifestations, including nausea, vomiting and diarrhea. Hypoglycemia is more likely when dulaglutide is used with sulfonylureas or insulin but is less pronounced when used as a monotherapy. Overall, dulaglutide exhibits a favorable safety profile.11
Conclusion
In the ever-evolving landscape of diabetes management, clinical inertia stands as a formidable challenge that demands innovative solutions. As medical professionals, recognizing the significance of early intensification and the role of incretin therapy with GLP1-RAs like dulaglutide is paramount. By understanding the nuances of clinical inertia, embracing evolving treatment paradigms, and effectively addressing patient hesitancy, we can pave the way for improved glycemic control and enhanced patient outcomes. The availability of GLP-1 RAs like dulaglutide may potentially bridge the gap between inertia, intensification and improved diabetes care.
References:
1. Okemah J, et al. Advances in Therapy 2018;35:1735–174.
2. Andreozzi F, et al. Diabetology & Metabolic Syndrome 2020;12:52.
3. Nathan DM, Buse JB, Davidson MB, et al. Diabetes Care 2009;32(1):193–203.
4. Davies MJ, et al. Diabetes Care 2022;45(11):2753–2786.
5. García-Pérez LE, Alvarez M, Dilla T, Gil-Guillén V, Orozco-Beltrán D. Diabetes Ther 2013;4(2):175–194.
6. de Lusignan S, Hinton W, Konstantara E, et al. BMC Health Serv Res 2019;19:284.
7. Guerci B, et al. Diabetes & Metabolism 2019;45:528–535.
8. Desouza C, et al. BMJ Open Diabetes Research & Care 2020;8(2):e001830.
9. Gerstein HC, et al. The Lancet 2019;394:121–130.
10. Kim S, et al. PLoS One 2022;17:e0273004.
11. Smith LL, et al. Pharmacy & Therapeutics 2016;41:357–360.
12. Latif W, et al. 2023 Mar 27. In: StatPearls [Internet]
13. Wettergreen SA, et al. Diabetes Spectr 2023;36:5–13.
PH-NP-LILLY-TRULIC-NR-HCP-000021 SEPTEMBER 2023
Clinical Inertia: Unraveling the hindrance
Clinical inertia or therapeutic inertia is a multifaceted challenge that can be caused by patient-related, physician-related, or healthcare system-related factors (Figure 1). It spans across various medical specialties, but its implications are especially pronounced in the realm of diabetes management. It can occur when healthcare providers fail to adequately adjust treatment plans despite clear indications that current therapies are insufficient in achieving desired clinical outcomes.1,2
Figure 1. Multiple factors that lead to clinical or therapeutic inertia. (Adapted from Okemah et al, 2018)On the other hand, patients who are reluctant to intensify treatment due to lack of awareness of the progressive nature of the disease or poor glycemic control also contribute a lot to the development of clinical inertia. While patient-related and physician-related causes are common, healthcare system-related factors in countries with limited resource are as challenging. In diabetes care, these often translate to delay in intensification of treatment, thereby allowing the disease to progress unchecked.1 Clinical inertia perpetuates the vicious cycle of escalating complications and reduced quality of life for patients. This phenomenon can lead to suboptimal control of blood glucose levels and subsequent complications.2
Intensification of Diabetes Therapy: Shifting Paradigms
Historically, the initiation of injectable therapy was often delayed until oral medications and lifestyle interventions yielded inadequate results.3 However, recent guidelines and evolving evidence suggest a more proactive approach to therapy intensification. Early initiation of injectable therapy, including GLP1-RAs, has shown promise in achieving and sustaining glycemic control, reducing the risk of complications, and minimizing the impact of clinical inertia.
The recent ADA/EASD Consensus Statement has brought focus to the use of glucose-lowering medications in consideration of clinically important factors, with greater emphasis on weight management as part of the holistic approach to management as well as broader recommendations for cardiorenal protection in people at high risk of cardiorenal disease. The need to reassess and modify treatment regularly (3-6 months) to avoid therapeutic inertia was also emphasized.4
Navigating Patient Hesitancy Towards Injectable Therapy
One of the key challenges in diabetes management is patient hesitancy toward injectable therapies.5 Fear of needles, concerns about the complexity of injections, and apprehensions about the perceived invasiveness of injectable treatments often deter patients from embracing these options. As medical professionals, fostering open and empathetic communication is vital to addressing these concerns and motivating patients to take the necessary steps towards improved glycemic control.5,6
Advantages of GLP1-RAs: Empowering Intensification
Among injectable therapies, GLP1-RAs have emerged as a cornerstone of intensification strategies being alternatives to basal insulin over the past 10 years. These are incretin mimetics that reproduce the effects of endogenous glucagon-like peptide-1 and, as such, stimulate glucose-dependent pancreatic insulin secretion and suppress pancreatic glucagon.7 The recent ADA and EASD consensus guidelines list GLP1-RAs as alternatives to insulin for treatment intensification in patients inadequately controlled with oral antidiabetic drugs.4 GLP-1 RAs also demonstrated significant benefits for both glycemic control and weight management over additional oral antidiabetic drugs (OADs) or insulin, respectively.8 Moreover, unlike traditional insulin therapy, GLP1-RAs offer distinct advantages in terms of convenience, efficacy and cardiovascular and renal benefits.9
The REWIND Trial has provided compelling evidence of the cardiovascular benefits associated with dulaglutide. Notably, this trial demonstrated a significant reduction in 3-point major cardiovascular event (MACE-3), a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, in patients with type 2 diabetes both with or without established CVD.9 These findings underscore the potential for GLP-1 RAs, particularly dulaglutide, to provide multifaceted benefits beyond glycemic control, further motivating early intervention and overcoming clinical inertia.9,10
An additional characteristic of dulaglutide resides in its prolonged half-life of approximately 5 days. This prolonged duration permits a once-weekly administration regimen, a notable advantage when juxtaposed with certain GLP1-RAs necessitating daily dosages.11,12 The less frequent treatment schedule offered by dulaglutide augments patient convenience and compliance, effectively alleviating the daily injection burden.13
Furthermore, within a comparative study gauging the temporal precision, usage accuracy, participant contentment, and preferences concerning pen devices employed for the once-weekly GLP-1 RAs dulaglutide, exenatide, and semaglutide, a substantial majority (75%) of participants evinced a clear inclination towards the dulaglutide device, signifying an overarching preference.13
Empirical evidence underscores the favorable attributes of dulaglutide in relation to other GLP-1 RAs. Notable investigations have demonstrated that dulaglutide garners superior reductions in HbA1c levels when pitted against liraglutide.12 Additionally, it exhibits heightened adherence rates in comparison to both exenatide and liraglutide.13
As a GLP-1 RA, the most common adverse effects are mild and transient gastrointestinal manifestations, including nausea, vomiting and diarrhea. Hypoglycemia is more likely when dulaglutide is used with sulfonylureas or insulin but is less pronounced when used as a monotherapy. Overall, dulaglutide exhibits a favorable safety profile.11
Conclusion
In the ever-evolving landscape of diabetes management, clinical inertia stands as a formidable challenge that demands innovative solutions. As medical professionals, recognizing the significance of early intensification and the role of incretin therapy with GLP1-RAs like dulaglutide is paramount. By understanding the nuances of clinical inertia, embracing evolving treatment paradigms, and effectively addressing patient hesitancy, we can pave the way for improved glycemic control and enhanced patient outcomes. The availability of GLP-1 RAs like dulaglutide may potentially bridge the gap between inertia, intensification and improved diabetes care.
References:
1. Okemah J, et al. Advances in Therapy 2018;35:1735–174.
2. Andreozzi F, et al. Diabetology & Metabolic Syndrome 2020;12:52.
3. Nathan DM, Buse JB, Davidson MB, et al. Diabetes Care 2009;32(1):193–203.
4. Davies MJ, et al. Diabetes Care 2022;45(11):2753–2786.
5. García-Pérez LE, Alvarez M, Dilla T, Gil-Guillén V, Orozco-Beltrán D. Diabetes Ther 2013;4(2):175–194.
6. de Lusignan S, Hinton W, Konstantara E, et al. BMC Health Serv Res 2019;19:284.
7. Guerci B, et al. Diabetes & Metabolism 2019;45:528–535.
8. Desouza C, et al. BMJ Open Diabetes Research & Care 2020;8(2):e001830.
9. Gerstein HC, et al. The Lancet 2019;394:121–130.
10. Kim S, et al. PLoS One 2022;17:e0273004.
11. Smith LL, et al. Pharmacy & Therapeutics 2016;41:357–360.
12. Latif W, et al. 2023 Mar 27. In: StatPearls [Internet]
13. Wettergreen SA, et al. Diabetes Spectr 2023;36:5–13.
PH-NP-LILLY-TRULIC-NR-HCP-000021 SEPTEMBER 2023